Late Conversion to Sirolimus or Everolimus After Pancreas Transplant.

BACKGROUND: Pancreas transplant is an effective treatment for insulin-dependent diabetic individuals with end-stage renal disease, yet immunosuppression-associated adverse events may adversely affect patient and graft survival. The aim of the study was to document whether mammalian target of rapamycin inhibitors (mTORi) are safe and effective as a second-line drug after pancreas transplant. METHODOLOGY: An observational single-center study was performed in a cohort of 490 simultaneous pancreas-kidney transplant and 45 pancreas-after-kidney transplant individuals after conversion to mTORi (n = 13) owing to adverse events of either tacrolimus or mycophenolate. RESULTS: mTORi conversion was performed 11.5 ± 10.1 (range, 1-28) months after pancreas transplant, mainly owing to cytomegalovirus infection and gastrointestinal intolerance. We frequently observed clinical complications after mTORi conversion, yet creatinine, eGFR, proteinuria, fasting plasma glucose, HbA1c, and C-peptide remained stable throughout the study (mean follow-up 8.2 ± 5, range 1-17) years, as did the lipid profile (P > .05). However, graft loss occurred in almost 20% of patients owing to chronic alterations. LIMITATIONS: The small number of patients and a single-center cohort were limitations of the study. CONCLUSIONS: Late mTORi conversion is a safe and effective approach when tacrolimus or mycophenolate-mediated adverse events occur after pancreas transplant.

HDL cholesterol levels and weight are the main determinants of subclinical atherosclerosis in the young with type 1 diabetes and suitable glycaemic control.

The aim of this study was to evaluate subclinical atherosclerosis and related factors in young type 1 diabetes (T1D) patients and healthy peers. Carotid intima-media thickness (cIMT) and anthropometric/laboratorial data were obtained for 83 T1D patients (mean age 19.5 ± 4.0 years, disease duration 9.8 ± 4.8 years) and for 36 matched healthy subjects. Considering all the participants as one group, male sex (p = 0.008), weight (p = 0.016) and T1D (p < 0.001) were positively associated with a higher cIMT. High-density lipoprotein (HDL) (p = 0.036) was negatively associated with cIMT in T1D. In the male T1D patients, HDL ≤47.5 mg/dL had a sensitivity of 87.5% and specificity of 57% (p = 0.035) in detecting those belonging to a higher cIMT tercile. In conclusion, weight and T1D were associated with increased cIMT. HDL levels ≤47.5 mg/dL were related to a higher cIMT in male T1D patients.

The evolution of diabetic chronic complications after pancreas transplantation.

Pancreas transplantation is an invasive procedure that can restore and maintain normoglycemic level very successfully and for a prolonged period in DM1 patients. The procedure elevates the morbimortality rates in the first few months following the surgery if compared to kidney transplants with living donors, but it offers a better quality of life to patients.Although controversial, several studies have shown the stabilization or the improvement of some of the chronic complications related to diabetes, as well as the extra number of years of life that patients submitted to a double pancreas-kidney transplantation may gain.Recent studies have demonstrated clashing outcomes regarding isolated pancreas transplantations, a fact which reinforces the need for a more discerning selection of patients for this procedure.

Kidney transplant in diabetic patients: modalities, indications and results.

BACKGROUND: Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy. CONCLUSION: Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.

Impact of pancreatic allograft function on 1-year survival rates after simultaneous pancreatic-renal transplant.

OBJECTIVES: Simultaneous pancreatic-renal transplant is an effective treatment for insulin-dependent patients with chronic renal failure. We sought to identify the main influences on pancreatic and patient survival rates after simultaneous pancreas-kidney transplants. PATIENTS AND METHODS: The 1-year patient and pancreas survival rates of 150 patients who had undergone simultaneous pancreas-kidney transplant were analyzed by the Cox proportional hazards regression model and the Kaplan-Meier method. Uni and multivariate analyses were performed in terms of transplant-, recipient-, and donor-related risk factors. RESULTS: At 1 year, patient and pancreatic allograft survival rates were 82% and 76.7%, respectively. Delayed graft function in the kidney (P = .001, HR 5.41), acute kidney rejection (P = .016, HR 3.36), and intra-abdominal infection (P < .0001, HR 4.15) were the main factors related to 1-year patient survival. Pancreatic allograft survival at 1 year was related to intra-abdominal infection (P < .0001, OR 12.83), vascular thrombosis (P = .002, OR 40.55), acute kidney rejection (P = .027, OR 3.06), donor sodium greater than 155 mEq/L (P = .02, OR 3.27), and dopamine administration exceeding 7.6 microg/kg/min (P = .046, OR 2.85). CONCLUSIONS: Delayed kidney allograft function and intra-abdominal infection had an important effect on both patient and pancreatic allograft survival rates.

Thrombotic microangiopathy after simultaneous pancreas-kidney transplantation.

Thrombotic microangiopathy (TMA) is rare after transplantation and is associated with a high incidence of kidney graft dysfunction. Between December 2000 and March 2006, 136 simultaneous pancreas-kidney transplantations were performed with an incidence of TMA of 5.1% (71.4% localized to kidney allograft). All cases were diagnosed during the first three months and were attributed to tacrolimus; 74% were women. Systemic TMA presented higher values of lactate dehydrogenase (2658 +/- 659 U/L vs. 1331 +/- 473 U/L, p = 0.04) and a greater decrease in hematocrit (45.8 +/- 17.7% vs. 19.2 +/- 6%, p = 0.02) than in localized TMA. Acute kidney rejection complicated almost 90% of the cases with 43% of kidney graft lost. Tacrolimus was switched to sirolimus and fresh-frozen plasma was administered. Creatinine clearance after a mean follow-up of two yr was 100.7 mL/min/1.73 m(2) and 57.9 mL/min/1.73 m(2) in patients with systemic and localized TMA, respectively. In conclusion, sirolimus is an alternative to TMA associated with tacrolimus.